The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: A randomised controlled trial

Petchey, William G., Hickman, Ingrid J., Duncan, Emma L., Prins, Johannes B., Hawley, Carmel M., Johnson, David W., Barraclough, Katherine, & Isbel, Nicole M. (2009) The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with chronic kidney disease: A randomised controlled trial. BMC Nephrology, 10(41).

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Abstract

BACKGROUND

Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation.

METHODS/DESIGN

This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study.

DISCUSSION

To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis.

TRIAL REGISTRATION

Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.

Impact and interest:

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ID Code: 94208
Item Type: Journal Article
Refereed: Yes
Keywords: Administration, Oral, Adult, Aged, Aged, 80 and over, Bone Density Conservation Agents/administration & dosage, Cholecalciferol/ administration & dosage, Double-Blind Method, Female, Humans, Inflammation/ complications/ prevention & control, Insulin Resistance, Kidney Failure, Chronic/ complications/ drug therapy, Male, Placebo Effect, Treatment Outcome, Vitamin D Deficiency/ complications/ drug therapy, Young Adult
DOI: 10.1186/1471-2369-10-41
ISSN: 1471-2369
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2009 Petchey et al; licensee BioMed Central Ltd
Copyright Statement: This is an Open Access article distributed under the terms of
the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 28 Mar 2016 23:58
Last Modified: 13 Dec 2016 00:56

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